We focus here on the modulation of thin filament activity by cardiac troponin I (cTnI) phosphorylation as an integral and adaptive mechanism in cardiac homeostasis and as a mechanism vulnerable to maladaptive response to stress. We discuss a current concept of cTnI function in the A-band region of the sarcomere, and potential signaling to cTnI i...

We focus here on the modulation of thin filament activity by cardiac troponin I (cTnI) phosphorylation as an integral and adaptive mechanism in cardiac homeostasis and as a mechanism vulnerable to maladaptive response to stress. We discuss a current concept of cTnI function in the A-band region of the sarcomere, and potential signaling to cTnI in a network involving the ends of the thin filaments at the Z-disk and the M-band regions. The cardiac sarcomere represents a remarkable set of interacting proteins that functions not only as a molecular machine generating the heartbeat, but also as a hub of signaling. We review how phosphorylation signaling to cardiac troponin I is integrated with parallel signals controlling excitation-contraction coupling, hypertrophy, and metabolism. Minimize

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis. Minimize

Genes for glycolytic and Calvin-cycle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of higher eukaryotes derive from ancient gene duplications which occurred in eubacterial genomes; both were transferred to the nucleus during the course of endosymbiosis. We have cloned cDNAs encoding chloroplast and cytosolic GAPDH from the early-branching ph...

Genes for glycolytic and Calvin-cycle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of higher eukaryotes derive from ancient gene duplications which occurred in eubacterial genomes; both were transferred to the nucleus during the course of endosymbiosis. We have cloned cDNAs encoding chloroplast and cytosolic GAPDH from the early-branching photosynthetic protist Euglena gracilis and have determined the structure of its nuclear gene for cytosolic GAPDH. The gene contains four introns which possess unusual secondary structures, do not obey the GT-AG rule, and are flanked by 2- to 3-bp direct repeats. A gene phylogeny for these sequences in the context of eubacterial homologues indicates that euglenozoa, like higher eukaryotes, have obtained their GAPDH genes from eubacteria via endosymbiotic (organelle-to-nucleus) gene transfer. The data further suggest that the early-branching protists Giardia lamblia and Entamoeba histolytica--which lack mitochondria--and portions of the trypanosome lineage have acquired GAPDH genes from eubacterial donors which did not ultimately give rise to contemporary membrane-bound organelles. Evidence that "cryptic" (possibly ephemeral) endosymbioses during evolution may have entailed successful gene transfer is preserved in protist nuclear gene sequences. Minimize

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis. Minimize

Objective: To quantify 18-fluorodeoxyglucose (FDG) accumulation in large vessels in patients with polymyalgia rheumatica by positron emission tomography (PET), and to compare these data with serological markers of inflammation.

Objective: To quantify 18-fluorodeoxyglucose (FDG) accumulation in large vessels in patients with polymyalgia rheumatica by positron emission tomography (PET), and to compare these data with serological markers of inflammation. Minimize

Arrhythmogenic substrate diagnosis has been achieved by electrophysiological studies and best localized by successful radiofrequency ablation. Pre-invasive localization procedures have been based on surface ECGs and more recently on biomagnetism, but in addition to these electric and magnetic signals a mechanical signal may be utilized: the init...

Arrhythmogenic substrate diagnosis has been achieved by electrophysiological studies and best localized by successful radiofrequency ablation. Pre-invasive localization procedures have been based on surface ECGs and more recently on biomagnetism, but in addition to these electric and magnetic signals a mechanical signal may be utilized: the initial site of contraction may be detected by phase analysis during radionuclide ventriculography. Generation of three-dimensional data set of phases is achieved by incorporating the new emission tomography technique. The performance of this modified phase analysis has been investigated for the detection of the normal contraction pattern during sinus rhythm, the arrhythmogenic substrate of the WPW syndrome and ventricular tachycardia, and further, to define the limitations of the method in experimental studies on pigs. In 30 out of 44 patients with normal sinus rhythm and no ventricular lesion, a characteristic phase pattern was found. Physiologically, the initial site of contraction appeared to be paraseptal and in the anterior wall of the right ventricle close to the apex. In 13 patients with WPW syndrome and in seven with ventricular tachycardia, the phase data were compared to the electrophysiological study. In 14 of 20 there was a complete match, in 3 of 20 a mechanical focus was found in the area adjacent to the electric focus. From experimental pig studies with simulated stimulation, a spatial precision of at least 20 mm was found at a pre-excitation of 20 ms. Thus, in three-dimensional phase analysis the normal contraction pattern of the ventricles can be visualized, and the arrhythmogenic substrates of WPW and ventricular tachycardia may be localized more precisely and reliably than by the surface ECG. Patients with mechanically induced atrial fibrillation, with a ventricular thrombus, or with non specific ECG abnormalities may benefit from this new tomographic technique which could assist subsequent invasion procedures. Minimize